Mastocytosis is a disease of disordered mast cell proliferation. It affects all ages, both sexes, and all ethnic groups. In some cases, mastocytosis has an aggressive and ultimately fatal course. Thus, our efforts are directed to improving diagnosis and treatment; and to clarify the etiology of this disease. Most recently we have described pulmonary, abdominal, and ovarian manifestations of aggressive mastocytosis. A successful approach to treatment for aggressive disease remains elusive. However, in vitro studies demonstrate that IFN-delta-1b does suppress human mast cell growth, where Interferon alpha-2b (IFNa-2b) does not. Studies on c-kit and the relevance of activating mutations which we first dentified (Asp816Val; Asp816Tyr)in mastocytosis patients are continuing. Data now indicates all patients with mastocytosis and an associated hematologic disorder have the point mutation Asp816Val in peripheral blood mononuclear cells. In contrast, adult patients with indolent mastocytosis may demonstrate this mutation only in skin lesions. Molecular studies are consistent with the conclusion that the Asp816 Val mutation is a somatic mutation and is not in germ line tissues. There is no consistent chromosomal abnormality in mastocytosis. However, cytogenic abnormalities are more frequent in aggressive disease and in those whose PBMC's show the Asp816Val mutaion. We have also now found that the Asp816Val mutation may be identified in CD34+ cells and is variably expressed in mast cells, meutrophils, monocytes, and lymphocytes.